Horizant (gabapentin enacarbil XR) / Azurity Pharma, Astellas, GSK - LARVOL DELTA

Identifying responders to gabapentin for the treatment of alcohol use disorder: an exploratory machine learning approach. (PubMed, Alcohol Alcohol) - "Baseline drinking levels and anxiety levels may be associated with the protracted withdrawal syndrome, previously implicated in the clinical response to gabapentin. However, these analyses underscore motivation for change and self-efficacy as predictors of clinical response to GE-XR, suggesting these established constructs should receive further attention in gabapentin research and clinical practice. Multiple studies using different machine learning methods are valuable as these novel analytic tools are applied to medication development for AUD."

Clinical • Journal • Addiction (Opioid and Alcohol) • Mood Disorders • Psychiatry

Treatment of Restless Legs Syndrome Improves Agitation and Sleep in Persons With Dementia: A Randomized Trial. (PubMed, J Am Med Dir Assoc) - "Our findings suggest a novel approach for nighttime agitation in persons with dementia: assessing for RLS and initiating interventions. Larger and longer trials are needed."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Movement Disorders • Restless Legs Syndrome • Sleep Disorder

Leveraging the Genetics of Psychiatric Disorders to Prioritize Potential Drug Targets and Compounds. (PubMed, medRxiv) - "We also observed genetic support for other commonly used psychotropics (e.g., clozapine, risperidone, duloxetine, lithium, and valproic acid). Opportunities for drug repurposing were revealed such as cholinergic drugs for ADHD, estrogens for depression, and gabapentin enacarbil for schizophrenia...Here we present a series of complimentary and comprehensive analyses that highlight the utility of genetics for informing drug development and repurposing for psychiatric disorders. Our findings present novel opportunities for refining psychiatric treatment."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Bipolar Disorder • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia • CYP2D6

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. (PubMed, J Clin Sleep Med) - "The following recommendations are intended as a guide for clinicians in choosing a specific treatment for RLS and PLMD in adults and children. Each recommendation statement is assigned a strength ("Strong" or "Conditional"). A "Strong" recommendation (i.e., "We recommend…") is one that clinicians should follow under most circumstances. The recommendations listed below are ranked in the order of strength of recommendations and grouped by class of treatments within each PICO question. Some recommendations include remarks that provide additional context to guide clinicians with implementation of this recommendation."

Clinical guideline • Journal • Chronic Kidney Disease • Movement Disorders • Nephrology • Obstructive Sleep Apnea • Pediatrics • Renal Disease • Respiratory Diseases • Restless Legs Syndrome • Sleep Disorder

Unraveling Shared Diagnostic Biomarkers of Fibromyalgia in Ankylosing Spondylitis: Evidence from Comprehensive Bioinformatic Analysis and Experimental Validation. (PubMed, J Inflamm Res) - "Gabapentin enacarbil was recognized as a potential therapeutic drug for AS-FM patients...Meanwhile, these results were confirmed in clinical samples. CETN3 and CACNA1E may become potential diagnostic biomarkers and therapeutic targets for patients with AS complicated by FM."

Biomarker • Journal • Ankylosing Spondylitis • CNS Disorders • Fatigue • Fibromyalgia • Immunology • Inflammatory Arthritis • Musculoskeletal Pain • Pain • Rheumatology • Seronegative Spondyloarthropathies • Sleep Disorder • CACNA1E • CACNG3

RLS TREATMENT REDUCES NIGHTTIME AGITATION AND INCREASES SLEEP DURATION IN OLDER ADULTS WITH ALZHEIMER'S DISEASE (SLEEP 2024) - "Support (if any): R01AG051588 UL1TR003015 Arbor - Horizant and placebo... Our results clearly show that RLS is an unrecog nized cause for nighttime agitation in older adults with dementia and that treatment of RLS with GEn, compared to placebo, sig nificantly reduced nighttime agitation and improved sleep"

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Restless Legs Syndrome • Sleep Disorder

Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder. (PubMed, Alcohol Alcohol) - "Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Sleep Disorder

Reductions in World Health Organization Risk Drinking Level Are Associated With Reductions in Alcohol Use Disorder Diagnosis and Criteria: Evidence From an Alcohol Pharmacotherapy Trial. (PubMed, J Addict Med) - "World Health Organization risk drinking level reductions correlate with Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria, providing further evidence for their use as endpoints in alcohol intervention trials, which has potential implications for broadening the base of AUD treatment."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Mental Retardation • Psychiatry

A COMPREHENSIVE UPDATE on the ADMET CONSIDERATIONS for α2δ CALCIUM CHANNEL LIGAND MEDICATIONS for TREATING RESTLESS LEGS SYNDROME. (PubMed, Expert Opin Drug Metab Toxicol) - "However, we highlight the linear kinetic of gabapentin enacarbil and pregabalin, differently from gabapentin. The use of α2δ ligands is associated to poor risk of augmentation. We still need new long-term safe and effective treatments, which could be developed along with our knowledge of RLS/WED pathophysiology."

Journal • Review • CNS Disorders • Insomnia • Mood Disorders • Movement Disorders • Musculoskeletal Pain • Pain • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Evaluation of Abuse Potential of HORIZANT Taken Alone and With Oxycodone in Healthy, Nondependent Recreational Opioid Users (clinicaltrials.gov) - P4 | N=110 | Completed | Sponsor: Azurity Pharmaceuticals

Combination therapy • New P4 trial • Addiction (Opioid and Alcohol)

An Abuse Potential Study of Orally Administered HORIZANT in Healthy, Non-dependent, Recreational Drug Users (clinicaltrials.gov) - P4 | N=86 | Completed | Sponsor: Azurity Pharmaceuticals

New P4 trial

Restless Legs Syndrome and Other Common Sleep-Related Movement Disorders. (PubMed, Continuum (Minneap Minn)) - "α2δ Ligands, such as gabapentin enacarbil, can be used for the initial treatment of restless legs syndrome (RLS) or in those who cannot tolerate, or have developed augmentation to, dopamine agonists...Dopaminergic medications can be very effective but often lead to augmentation, which limits their long-term use. Other sleep-related movement disorders to be aware of are sleep-related rhythmic movement disorder, nocturnal muscle cramps, sleep-related propriospinal myoclonus, sleep bruxism, and benign myoclonus of infancy."

Journal • Cardiovascular • Dental Disorders • Hematological Disorders • Movement Disorders • Restless Legs Syndrome • Sleep Disorder

Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives. (PubMed, Curr Pain Headache Rep) - "In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture."

Journal • Review • Anesthesia • Neuralgia • Pain

Gabapentin as a Pre-emptive Analgesic in Oral and Maxillofacial Surgical Procedures (clinicaltrials.gov) - P4 | N=0 | Withdrawn | Sponsor: Massachusetts General Hospital | N=30 ➔ 0 | Unknown status ➔ Withdrawn

Enrollment change • Trial withdrawal • Pain

Network-Based Data Analysis Reveals Ion Channel-Related Gene Features in COVID-19: A Bioinformatic Approach. (PubMed, Biochem Genet) - "Drug-target enrichment analysis showed that the relevant drugs targeting the hub genes CACNA2D1, CACNA1A, CACNA1E, KCNA2 and KCNA5 were gabapentin, gabapentin enacarbil, pregabalin, guanidine hydrochloride and 4-aminopyridine. The results of this study provide a valuable basis for exploring the mechanisms of ion channel genes in COVID-19 and clues for developing therapeutic strategies for COVID-19."

Journal • Ataxia • CNS Disorders • Developmental Disorders • Infectious Disease • Mental Retardation • Movement Disorders • Nicotine Addiction • Novel Coronavirus Disease • Psychiatry • Respiratory Diseases • CACNA1A • FOXC1 • GATA2 • MIR129 • MIR129-2 • MIR146A • MIR27A • MIR335 • MIRLET7B • TRPC1

Gabapentin Implicated in Overdose Deaths (RheumNow) - "Recent FDA and MMWR warnings suggest that gabapentin was present and implicated in almost 10% of US overdose deaths between 2019 and 2020. This CDC report also stated that gabapentin was the cause of the death in half of these cases. Despite its FDA approval for the management of seizures and pain from herpes zoster, off-label use of gabapentin in pain and neuropathy resulted in a doubling of gabapentin prescriptions from 13 to 27 per 1000 insurance claims between 2009 and 2016. In 2019 gabapentin was teh 7th most prescribed drug in the USA."

Online posting

How I Do It: Treating Severe Refractory and Augmented RLS. (PubMed, Chest) - "RLS can generally be well treated with medications such as alpha-2-delta calcium channel ligands (A2Ds) gabapentin, pregabalin, gabapentin enacarbil or, if these are poorly tolerated or lack efficacy, dopamine agonists (DAs), pramipexole, ropinirole or rotigotine. However, given the profound rebound RLS and insomnia that occurs with even small dose reductions of DAs, the initial change should be the addition of one of these alternate treatments. Once adequate doses, or symptom relief, are achieved with the second agent, subsequent very slow down-titration and discontinuation of the DA is often possible and can lead to dramatic long-term relief of RLS symptoms and improvement in sleep."

Journal • Review • CNS Disorders • Hematological Disorders • Immunology • Insomnia • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • KEAP1

Treatment initiation and utilization patterns of pharmacotherapies for early-onset idiopathic restless legs syndrome. (PubMed, Sleep Med) - "Ropinirole, pramipexole, and gabapentin were initiated most often for early-onset idiopathic RLS. FDA-approved agents for RLS, including gabapentin enacarbil and rotigotine, were used less frequently. In general, persistence was low for all RLS study drugs examined."

Journal • Movement Disorders • Restless Legs Syndrome • Sleep Disorder

Orthostatic Tremor Awareness Can Lead to Better Diagnoses - "Research into other types of treatments is ongoing, but uncertainty about the cause of orthostatic tremor complicates matters, says Dr. Hassan. 'When we look at brain scans or blood tests of patients with this type of tremor, we don't see any obvious abnormality,' says Dr. Hassan. One theory suggests it stems from a problem in the cerebellum, which is the balance center at the back of the brain, but tremors from disorders of the cerebellum are usually slow, while orthostatic tremors are fast. 'There seems to be some dysfunction there, but it still isn't completely understood,' Dr. Hassan says."

Media quote

Initiation of Pharmacotherapies for Newly Diagnosed Early-Onset Idiopathic Restless Legs Syndrome from 2012-2019 (ISPOR 2022) - "Pharmacotherapies initiated most often were: ropinirole (46.8%), pramipexole (25.2%), and gabapentin (21.1%). Levodopa/carbidopa (2.1%), pregabalin (1.3%), gabapentin enacarbil (0.7%), and rotigotine (0.4%) were initiated less often... In this nationally representative sample of privately insured adults, pharmacotherapies initiated for newly diagnosed early-onset idiopathic RLS were predominantly FDA-approved dopamine agonists followed by off-label gabapentin. Limited use of FDA-approved gabapentinoids, pregabalin and gabapentin enacarbil, warrants further investigation of long-term RLS treatment utilization."

CNS Disorders • Depression • Hypertension • Insomnia • Mood Disorders • Movement Disorders • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Restless Legs Syndrome • Sleep Disorder

Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer's Disease (clinicaltrials.gov) - P4 | N=156 | Recruiting | Sponsor: University of Texas at Austin | Trial completion date: Mar 2022 ➔ Mar 2023 | Trial primary completion date: Mar 2021 ➔ Aug 2022

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Movement Disorders • Restless Legs Syndrome • Sleep Disorder

Nonopioid drugs for pain. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Immunology • Neuralgia • Osteoarthritis • Pain • Rheumatology

XP-IIT-0034: The Effect of Horizant (Gabapentin Enacarbil) on Augmentation (clinicaltrials.gov) - P=N/A | N=10 | Completed | Sponsor: University of Missouri-Columbia | N=19 ➔ 10

Enrollment change • Movement Disorders • Restless Legs Syndrome • Sleep Disorder

Effects of Gabapentin Enacarbil on Postoperative Pain After Hip and Knee Arthroplasty: A Placebo-controlled Randomized Trial. (PubMed, Clin J Pain) - "We did not identify statistically significant or clinically meaningful differences in our primary and secondary outcomes related to perioperative use of gabapentin enacarbil in patients having primary hip or knee arthroplasties."

Journal • Orthopedics • Pain

Drugs for alcohol use disorder. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Addiction (Opioid and Alcohol)